Bacterial endotoxins have long been known to deplete an animal of its carbohydrate reserves. The mechanism(s) responsible, however, remain to be elucidated. In this study characterization of glucose and glycogen metabolism in endotoxin poisoned mice will be made by measuring the time and dose effects of endotoxin on the incorporation of labeled precursors into glucose and glycogen as well as the time and dose effects of endotoxin on enzymes of the glycogen cycle, glycogen synthase and glycogen phosphorylase. In addition, activation of glycogen synthase by glucose, glucocorticoids and 30 C incubation will be studied in poisoned animals. A survey of other factors which might contribute to carbohydrate loss during endotoxemia will also be made. The effect of endotoxin on lysosomal glycosidases in serum, liver homogenates, and lysosome preparations from poisoned mice will be evaluated. The possible contribution of impaired energy metabolism to reduced carbohydrate synthesis will also be investigated. Pending the outcome of preliminary experiments, the role of catecholamines and other mediators in sugar loss from the liver during endotoxin shock will be studied. Finally, an extension of these studies to include an investigation of carbohydrate homeostasis in intact parenchymal cells isolated from mouse liver as well as in mice infected wtih Salmonella typhimurium will, hopefully, enhance our understanding of the role of endotoxin in the pathogenesis of gram negative sepsis.